Demonstrated virological efficiency of Islatravir + Ulonivirin with S24 dual therapy in a phase 2B test

Ulonivirin (ULO) is a new non -nucleosidic inhibitor of the reverse transcriptase. Furthermore, with long action duration, allowing a weekly socket. Similarly, Islatravir (ISL). Consequently, on the other hand, is a nucleosidic inhibitor of the transcriptase transcriptase, also with long half-life, but whose toxicity on total lymphocytes, and in particular CD4+ T lymphocytes (CD4+), has already been reported in high doses.

The aim of this trial was to study the effectiveness of this maintenance dual therapy administered once a. Meanwhile, week in patients living with HIV-1.

Patients virologically controlled for at least six months thanks to the Fixed Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) association. and without resistance transfer, were distributed randomly in four groups: 3 receiving ISL at 20 mg per week combined at different doses of ULO (100, 200 and 400 mg/week) and a fourth group continuing to process treatment B/F/TAF.

Due demonstrated virological efficiency islatravir + to the lymphocytic toxicity observed with the ISL, the test was interrupted prematurely. However, patients continued to be followed, in particular to assess the reversibility of this toxicity.

In total. 161 patients were included (121 in ISL + ULO groups, 40 in group B/F/TAF), with a median age of 45 and a median CD4 + rate for the inclusion of 748/mm³. At the end of the study, 113 participants reached week 24 (S24). Among them. all have maintained a charge virale The plasma viral load is the number of viral particles contained in a sample of blood or other container (saliva, LCR, sperm, etc.). For HIV. the viral load is used as a marker in order to follow the progression of the disease and measure the effectiveness of treatments. The level of viral load, but even more the CD4 rate, participate in the antiretroviral treatment decision. demonstrated virological efficiency islatravir + Undetectable, and no virological failure – defined by two consecutive plasma viral charges ≥ 200 copies/ml – has been reported.

The rates of side effects (IS) were comparable between the ISL + ULO. B/F/TAF groups (77 % vs 68 %), as well as IS related to treatment (17 % vs 10 %) and treatment interruptions for IS (3 % vs 0 %). In S24. the average drop in lymphocytes and CD4 + was 27 % and 24 % respectively in ISL + ULO groups, against 3 % and 1 % in group B/F/TAF. Recovery of lymphocyte and CD4 + rates was observed in all participants in ISL + ULO groups, 24 weeks after stopping dual therapy.

ISL + ULO dual therapy confirms its virological efficiency at week 24 by maintaining an undetectable viral load. However, as in other studies using 20 mg of ISL per week, a reversible lymphocytic depletion demonstrated virological efficiency islatravir + has been observed. These results motivate the continuation of the tests, this time with a weekly dose of ISL reduced to 2 mg.

According to Molina JM et al. Abstr. 1663, updated

This article was previously published in the E-Journal of the Infectiologist’s letter on the occasion of the IAS 2025. We reproduce it here with their kind authorization.